Kinome‐Wide Synthetic Lethal Screen Identifies PANK4 as a Modulator of Temozolomide Resistance in Glioblastoma DOI Creative Commons
Viviana Vella, Angeliki Ditsiou,

Anna Chalari

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(15)

Published: Feb. 14, 2024

Abstract Temozolomide (TMZ) represents the cornerstone of therapy for glioblastoma (GBM). However, acquisition resistance limits its therapeutic potential. The human kinome is an undisputable source druggable targets, still, current knowledge remains confined to a limited fraction it, with multitude under‐investigated proteins yet be characterized. Here, following kinome‐wide RNAi screen, pantothenate kinase 4 (PANK4) isuncovered as modulator TMZ in GBM. Validation PANK4 across various TMZ‐resistant GBM cell models, patient‐derived lines, tissue samples, well vivo studies, corroborates potential translational significance these findings. Moreover, expression induced during treatment, and associated worse clinical outcome. Furthermore, Tandem Mass Tag (TMT)‐based quantitative proteomic approach, reveals that abrogation leads significant downregulation host central roles cellular detoxification response oxidative stress. More specifically, cells undergo genotoxic stress exposure, depletion crucial event can lead accumulation intracellular reactive oxygen species (ROS) subsequent death. Collectively, previously unreported role mediating unveiled.

Language: Английский

Coenzyme A biosynthesis: mechanisms of regulation, function and disease DOI
Samuel A. Barritt, Sarah DuBois-Coyne, Christian C. Dibble

et al.

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(6), P. 1008 - 1023

Published: June 13, 2024

Language: Английский

Citations

21
Kinome‐Wide Synthetic Lethal Screen Identifies PANK4 as a Modulator of Temozolomide Resistance in Glioblastoma DOI Creative Commons
Viviana Vella, Angeliki Ditsiou,

Anna Chalari

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(15)

Published: Feb. 14, 2024

Abstract Temozolomide (TMZ) represents the cornerstone of therapy for glioblastoma (GBM). However, acquisition resistance limits its therapeutic potential. The human kinome is an undisputable source druggable targets, still, current knowledge remains confined to a limited fraction it, with multitude under‐investigated proteins yet be characterized. Here, following kinome‐wide RNAi screen, pantothenate kinase 4 (PANK4) isuncovered as modulator TMZ in GBM. Validation PANK4 across various TMZ‐resistant GBM cell models, patient‐derived lines, tissue samples, well vivo studies, corroborates potential translational significance these findings. Moreover, expression induced during treatment, and associated worse clinical outcome. Furthermore, Tandem Mass Tag (TMT)‐based quantitative proteomic approach, reveals that abrogation leads significant downregulation host central roles cellular detoxification response oxidative stress. More specifically, cells undergo genotoxic stress exposure, depletion crucial event can lead accumulation intracellular reactive oxygen species (ROS) subsequent death. Collectively, previously unreported role mediating unveiled.

Language: Английский

Citations

2